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Cited by 34Chronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and TreatmentCell Adhesion Molecules Research

Underexpression of RhoH in Hairy Cell Leukemia

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Galiègue-Zouitina, Sylvie, Delestré, Laure, Dupont, Caroline, Troussard, Xavier, Shelley, Carl Simon·2008·Cancer Research
DOI 10.1158/0008-5472.can-07-5661
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Abstract

The cause of hairy cell leukemia (HCL) is unknown. Current treatments seem effective only for a limited period of time. In addition, a significant proportion of patients remain refractive to all treatment options. These considerations indicate the need to develop alternative therapeutic strategies for HCL. Here, we report that HCL is characterized by underexpression of RhoH. In vitro reconstitution of RhoH expression inhibits the aberrant adhesion and transendothelial migration that drives disease pathogenesis. In an in vivo model of HCL, RhoH reconstitution limits malignant progression and protects against mortality. These findings provide the proof of principle that RhoH reconstitution represents a potential new approach to the treatment of HCL. [Cancer Res 2008;68(12):4531–40]

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  • Lymphocytes from HCL patients demonstrate approximately 3-4 fold lower RHOH mRNA expression compared to a variety of other lymphoid diseases.

    “Lymphocytes isolated from HCL patients demonstrate app. 3–4 fold lower RHOH mRNA expression compared to a variety of other diseases of the lymphoid system, such as Burkitt lymphoma, plasmocytoma or T-cell acute lymphoblastic leukaemia.”

    From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [55]

    The Results (page not provided) report 3.4-fold lower RhoH mRNA in HCL cell lines than in cell lines from the listed lymphoid diseases. The claim instead assigns that comparison to lymphocytes isolated from HCL patients. For patient-derived lymphocytes, the Results report a 5.2-fold reduction compared with healthy donors, not a 3–4-fold reduction compared with those diseases. (LLM, conf=0.93)

    Experimental — accuracy not yet measured

  • Overexpression of RhoH in hairy cell leukaemia reduces the transformation potential.

    “The recent finding that overexpression of RhoH in hairy cell leukaemia reduces the transformation potential [55] might stimulate a new interest in the functioning of RhoH on a molecular level.”

    From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [55]

  • The lower RHOH mRNA expression in HCL is caused by transcriptional repression of the RHOH promoter.

    “The lower mRNA expression was found to be caused by transcriptional repression of the RHOH promoter [55].”

    From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [55]

  • In an in vivo xenograft model, RhoH reconstitution inhibits malignant progression and reduces tumour burden by 70%.

    “In an in vivo xenograft model, RhoH reconstitution leads to the inhibition of malignant progression. The tumour burden of the mice was reduced by 70% suggesting that elevated levels of RhoH protected the animals against mortality [55].”

    From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [55]

  • RhoH reconstitution reduces transendothelial migration in a transwell assay.

    “In a transwell assay, the authors could demonstrate that RhoH reconstitution reduced transendothelial migration, a central process in the pathogenesis of the disease.”

    From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [55]

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Authors
Galiègue-Zouitina, S., Delestré, L., Dupont, C., Troussard, X., & Shelley, C. S.
Affiliations
  • 1Institut National de la Santé et de la Recherche Medicale U.837, Centre Jean-Pierre Aubert, Institut de Recherches sur le Cancer de Lille and Université Droit et Santé de Lille II, Lille, France;
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Caen Normandie (FR)
  • Harvard University (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2008-06-15
Volume
68
Issue
12
Pages
4531-4540
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-07-5661
OpenAlex
W2116364298
Cited by
34
References
1
Citations by year
2024: 4 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 1 · 2016: 2 · 2015: 2 · 2013: 5 · 2012: 1
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Hairy Cell Leukemia Research Foundation
Topics
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
hairy cell leukemia, RhoH, cell adhesion, transendothelial migration, pathogenesis, malignant progression, treatment options
MeSH terms
Animals, Cell Adhesion, Cell Movement, Chronic Disease, Flow Cytometry, Humans, Leukemia, Hairy Cell, Leukocytes, Lymphocytes, Lymphoma, Male, Promoter Regions, Genetic, Spleen, Splenic Neoplasms, Thrombocythemia, Essential, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Blotting, Western, Mice, SCID, rho GTP-Binding Proteins, Xenograft Model Antitumor Assays, CD11c Antigen, Cell Proliferation, Mice

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